Is the narrative the message? The relationship between suicide-related narratives in media reports and subsequent suicides.

OBJECTIVES: When journalists report on the details of a suicide, the way that they contextualize the meaning of the event (i.e. the 'narrative') can have significant consequences for readers. The 'Werther' and 'Papageno' narrative effects refer to increases and decreases in suicides across populations following media reports on suicidal acts or mastery of crises, respectively. The goal of this study was to investigate the impact of these different narrative constructs on subsequent suicides. METHODS: This study examined the change in suicide counts over time in Toronto, Canada. It used latent difference score analysis, examining suicide-related print media reports in the Toronto media market (2011-2014). Articles (N = 6367) were coded as having a potentially harmful narrative if they described suicide in a celebrity or described a suicide death in a non-celebrity and included the suicide method. Articles were coded as having potentially protective narratives if they included at least one element of protective content (e.g. alternatives to suicide) without including any information about suicidal behaviour (i.e. suicide attempts or death). RESULTS: Latent difference score longitudinal multigroup analyses identified a dose-response relationship in which the trajectory of suicides following harmful 'Werther' narrative reports increased over time, while protective 'Papageno' narrative reports declined. The latent difference score model demonstrated significant goodness of fit and parameter estimates, with each group demonstrating different trajectories of change in reported suicides over time: (χ2[6], N = 6367) = 13.16; χ2/df = 2.19; Akaike information criterion = 97.16, comparative fit index = 0.96, root mean square error of approximation = 0.03. CONCLUSION: Our findings support the notion that the 'narrative' matters when reporting on suicide. Specifically, 'Werther' narratives of suicides in celebrities and suicides in non-celebrities where the methods were described were associated with more subsequent suicides while 'Papageno' narratives of survival and crisis mastery without depictions of suicidal behaviours were associated with fewer subsequent suicides. These results may inform efforts to prevent imitation suicides.

Youth voices and experiences regarding a school-based cognitive behavioral therapy skills intervention: lessons for future engagement and adaptation.

BACKGROUND: The Cognitive Behavioral Therapy Skills Intervention (or CBTSI) aims to build mental health literacy and knowledge, allowing youth to build resilience and improve mental health broadly. In Ontario, Canada, youth voice is scant and European studies have largely reported on youth factors supporting stigma reduction, help-seeking intentions and overall satisfaction with a given intervention. Process evaluations and implementation that underpin what youth require to embrace mental health literacy interventions, particularly those that embed key learning principles in the everyday curriculum, have not been broached. The goal of this study is to understand both barriers and facilitators to engagement with the CBTSI (an intervention novel in itself because of the combined mental health plus cognitive behavior therapy (CBT) skills principles embedded in literacy) and the resources and structures that students report requiring, to fully engage with such an intervention. METHODS: Student focus groups were conducted utilizing qualitative interviews that were analyzed thematically. Analysis was informed using principles of pragmatism and analyzed inductively using thematic analysis (Braun and Clarke, Qual Res Psychol 3:77-101, 2006), first looking at the whole and then coding for themes, within an interpretivist framework. Youth were in middle school (grade 7 and 8) in Toronto, Canada who had received the CBTSI. Face to face interview guides with iterative questioning were conducted in February of 2020, and these interviews were audio-recorded and professionally transcribed. Teachers randomly chose a subset of youth whose parents consented to the research to ensure ethno-racial similarity to classroom demographics. RESULTS: There were eight groups with sixty students who participated. Students were 12 to 14 years of age. Major themes were identified: maximizing the opportunities for involvement and self-determination created an atmosphere where confidence and self-compassion could flourish, signalling to the students that they understood and were able to deploy the strategies they were taught; students expressed that the intervention needs to be adapted to enhance personal dignity, respecting both individual wishes and goals in light of the variability in student reported mental health. A model explains the structures and adaptations required to maximize learning based on youth feedback. INTERPRETATION: Mental health literacy incorporating CBT is a promising population-based health promotion intervention. Future adaptations and implementation decisions regarding the CBTSI need to address the wishes and experiences of these youth. Youth voice in this study explored factors that prevent and promote the uptake of the key lessons within the context of existing variability in student mental health that is often found within the context of a regular classroom. The results should be used to adapt the CBTSI as it is disseminated more broadly.

Inflammatory markers, brain-derived neurotrophic factor, and the symptomatic course of adolescent bipolar disorder: A prospective repeated-measures study.

BACKGROUND: Numerous studies have found elevated pro-inflammatory markers and reduced brain-derived neurotrophic factor (BDNF) during symptomatic episodes of bipolar disorder (BD) in adults. There is a paucity of research examining these markers in youth with BD, or longitudinally in any BD age group. METHODS: 79 adolescents, ages 13-19 years, were enrolled, including 43 symptomatic adolescents with BD and 36 age-matched healthy controls (HC). Blood samples were collected from all participants at intake, and repeatedly from BD participants at pre-specified intervals over the course of two years. Serum was assayed for levels of pro-inflammatory markers (c-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor alpha [TNF-α]), BDNF and the anti-inflammatory marker, IL-10. Week-by-week severity of mood symptoms was assessed using semi-structured interviews. RESULTS: Adolescents with BD provided an average of 4.6 blood samples, on average every 5.0 months. During the most severe symptomatic interval (i.e., highest sum of mood symptom scores) among BD adolescents, levels of CRP (p = 0.01) and pro- to anti-inflammatory ratios (CRP/IL-10; p < 0.001 and IL-6/IL-10; p = 0.046) were significantly greater, and IL-10 levels (p = 0.004) were significantly lower, vs. HC. There were no differences between BD and HC in IL-6, TNF-α or BDNF. Within BD participants, higher BDNF (p = 0.01) and IL-10 levels (p = 0.001) significantly predicted greater burden of mood symptoms over the subsequent epoch. Moreover, higher CRP levels (p = 0.009) at intake predicted greater time to recovery from the index symptomatic episode. CONCLUSIONS: In the first repeated-measures study on this topic in adolescents with BD, we found evidence that CRP, an inexpensive and ubiquitous blood test, may be useful in predicting the prospective course of BD symptoms. Future larger studies are warranted.

Functional outcomes with bright light in monotherapy and combined with fluoxetine in patients with major depressive disorder: Results from the LIFE-D trial.

BACKGROUND: Bright light therapy has been shown to improve depressive symptoms in patients with nonseasonal major depressive disorder (MDD) but there are few studies examining functional outcomes. METHODS: We examined secondary functional outcomes in the 8-week randomized, placebo-sham-controlled LIFE-D trial comparing light therapy, fluoxetine, and the combination in patients with nonseasonal MDD. Functional assessments included the Sheehan Disability Scale (SDS) and, for employed participants, the Lam Employment Absence and Productivity Scale (LEAPS). Analysis of covariance (ANCOVA) was conducted with SDS and LEAPS change scores from baseline to week 8 as dependent variables, treatment modality (light, fluoxetine) as an independent variable, and baseline SDS and LEAPS scores as covariates. RESULTS: Of 122 randomized participants, SDS data were available for 105 and LEAPS data for 70. For the SDS, there were no interaction effects, but there was a significant small- to medium-sized main effect of light treatment on total SDS scores with corresponding significant effects in the Social Life and Family Life domains, but not in the Work/Study domain. There were no significant interaction or main effects with LEAPS scores. CONCLUSION: Light therapy significantly improved social and family life functioning in patients with MDD. However, work functioning was not significantly improved despite large effect sizes; these results were limited by low statistical power because of small sample sizes. Future studies should use longer treatment durations and be powered to detect clinically relevant differences in functional outcomes.

The Impact of a Harry Potter-Based Cognitive-Behavioral Therapy Skills Curriculum on Suicidality and Well-being in Middle Schoolers: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the impact of a Harry Potter-based mental health literacy curriculum, imparting cognitive behavioral therapy (CBT) skills, on suicidality and well-being in middle-schoolers. METHODS: Students (aged 11-14; grades 7-8) who received a 3-month teacher-delivered intervention embedded in the language arts curriculum (N=200) were compared to a wait-list control group (N=230) in the largest urban school board in Canada. Suicidality defined as a composite measure of self-reported suicidal ideation and attempts [primary outcome], self-reported emotion dysregulation, interpersonal chaos, confusion about self, and impulsivity [Life Problems Inventory (LPI)] and self-reported depression and anxiety symptoms [Revised Child Anxiety and Depression Scale (RCADS)] were the outcomes of interest. Measurements occurred prior to and after curriculum delivery with independent t-tests used to compare mean change scores between groups clustered by class. RESULTS: Thirty-seven English teachers in 46 classes across 15 schools comprised the planned study cohort. Composite suicidality scores were significantly worse in the control than intervention group at endpoint (0.05±0.54 vs. 0.17±0.47, t= -2.60, df=428, p=0.01). There were also significant improvements in LPI and RCADS scores in the intervention group compared to controls (LPI:-3.74±7.98 vs. 1.16±10.77 t=5.28, df=428, p<.001; RCADS: (-3.08±5.49 vs. -1.51±6.53 t=2.96, df=429, p=0.01). Sub-analyses revealed that these improvements were largely driven by a significant difference in scores in girls. LIMITATIONS: Sample size constraints as study terminated prematurely during COVID pandemic. CONCLUSIONS: This study demonstrates significant improvement in suicidality, emotional regulation, self-concept, interpersonal difficulties, depression and anxiety in youth, particularly girls following this intervention. Replication studies in larger samples are needed to confirm these results.

The association between placebo arm inclusion and adverse event rates in antidepressant randomized controlled trials: An examination of the Nocebo Effect.

BACKGROUND: Antidepressant efficacy is influenced by patient expectations and, in randomized controlled trials (RCTs), the probability of receiving a placebo. It is unclear whether tolerability demonstrates a similar pattern. This study aimed to determine whether study design influences adverse event (AE) rates in antidepressant trials for subjects receiving active treatment or placebo. METHODS: RCTs comparing one antidepressant to another antidepressant, placebo, or both in major depressive disorder (MDD) (1996-2018) were retrieved from Medline and PsycINFO. Clinicaltrials.gov was searched for unpublished trials. Of 1,997 studies screened, 77 trials were included. Studies were classified as drug-drug, drug-drug-placebo, or drug-placebo based on design and overall number of subjects experiencing any AE was recorded. Subgroup meta-analysis of proportions and meta-regression techniques were used to compare AE rates across study designs in patients receiving active antidepressant treatment and placebo. RESULTS: Among the actively treated, AE rates were lower in drug-drug trials (58.5%) compared to drug-drug-placebo (75.7%) and drug-placebo (76.4%) (the model reported coefficients for percent differences between AE rates of different study designs were B=17.0, p<0.001 and B=17.8, p<0.001, respectively). AE rates in patients receiving placebo were not different between study designs. LIMITATIONS: The present study is limited by the diverse range of study populations, variability in reporting of AEs, and specific antidepressants employed in the included trials. CONCLUSIONS: The inclusion of a placebo arm in the study design was unexpectedly associated with higher rates of AEs among patients receiving active medication in antidepressant trials. This observation has important implications for interpretation of trial tolerability findings.

Preliminary Investigation of a Novel Cognitive Behavioural Therapy Curriculum on the Wellbeing of Middle Schoolers.

OBJECTIVES: A number of school-based interventions for preventing and attenuating symptoms of anxiety and depression in youth have been developed worldwide but evidence of their effectiveness is mixed. None of these curricula stem from existing children's literature, however, the Harry Potter (HP) series has been identified as potentially imparting Cognitive Behavioural Therapy concepts. METHODS: This study aimed to broadly capture, at an interim stage, the feasibility of a pilot HP curriculum aimed at imparting CBT skills to middle-schoolers in order to inform full development of the curriculum. The study design further included a non-randomized, Group (HP; Control) by Time (Baseline, Post-Intervention, Follow-up) mixed factorial approach retrospectively examining change in scores on a "Well-Being and Resiliency Survey" (WBRS) which assessed multiple symptomatic and social domains. RESULTS: In total, 232 grade seven and eight students participated in the curriculum over two years with no dropouts. Compared to 362 controls, there were no significant differences in WBRS scores between groups at post or one-year follow-up. CONCLUSIONS: This pilot study demonstrated the feasibility of rapid and broad implementation of the intervention. Preliminary analyses showed no indication of effectiveness which may be the product of the intervention being in an interim stage during the study period and/or the retrospective design and limitations in data quality. Specifically, these results suggest that the WBRS may be a suboptimal instrument for measuring the effectiveness of this intervention. A prospective trial of the complete, revised curriculum with validated measures is required to provide an adequately assessment of its impact.

OBJECTIFS: Un certain nombre d'interventions en milieu scolaire visant à prévenir et à atténuer les symptômes d'anxiété et de dépression chez les adolescents ont été mises au point dans le monde, mais les données probantes de leur efficacité sont partagées. Aucun de ces programmes d'études n'est issu de la littérature pour enfants existante, pourtant, la série des Harry Potter (HP) a été reconnue transmettre potentiellement des concepts de la thérapie cognitivo-comportementale (TCC). MÉTHODES: La présente étude visait à appréhender largement, à un stade préliminaire, la faisabilité d'un programme pilote HP destiné à transmettre des compétences de TCC aux élèves de premier cycle du secondaire afin d'éclairer l'élaboration complète du programme. La méthode de l'étude comprenait en outre un groupe non randomisé (HP, témoin) une chronologie (ligne de départ, post-intervention, suivi), une approche factorielle mixte examinant rétrospectivement le changement des scores à un « Sondage sur le bien-être et la résilience ¼ (SBER) qui évaluait les multiples domaines symptomatiques et sociaux. RÉSULTATS: En tout, 232 élèves de 7e et de 8e année ont participé au programme durant deux ans sans abandons. Comparativement aux 362 témoins, il n'y avait pas de différences significatives des scores de SBER entre les groupes au suivi d'un an ou après. CONCLUSIONS: Cette étude pilote a démontré la faisabilité de la mise en œuvre rapide et élargie de l'intervention. Les analyses préliminaires n'ont indiqué aucune efficacité qui puisse être le produit du stade préliminaire de l'intervention durant la période de l'étude et/ou de la méthode rétrospective et des limitations de la qualité des données. Spécifiquement, ces résultats suggèrent que le SBER peut être un instrument sous-optimal pour mesurer l'efficacité de cette intervention. Un essai prospectif du programme complet révisé avec des mesures validées est nécessaire pour obtenir une évaluation adéquate de son effet.

Antidepressant-placebo differences for specific adverse events in major depressive disorder: A systematic review.

BACKGROUND: Adverse events (AEs) are known to occur while patients are treated with placebos, part of the so-called nocebo effect. Yet evidence is limited regarding the likelihood that specific AEs occurring with antidepressant treatment are or are not due to nocebo effects. METHODS: This study identified 56 placebo-controlled, randomized controlled trials (RCTs) of antidepressant monotherapy for adults with major depressive disorder that reported AE rates in sufficient detail for comparison. Poisson regression analyses compared rates of AEs according to antidepressant class weighted by study population to determine which separated from placebo. A "nocebo index" was also calculated (with 0 defined as the lowest rate and 1 or higher indicating the same or greater rate of an AE in the placebo group). RESULTS: Numerous AEs did not differ statistically between antidepressant classes and placebo including worsening psychiatric symptoms, all forms of pain, weight gain and respiratory symptoms. Nevertheless, a number of AEs were significantly more common in antidepressants than placebos across multiple antidepressant classes. These were predominantly neurological, sexual and anticholinergic effects. Several AEs that separated statistically between antidepressants and placebos nevertheless had moderate nocebo indices (≥0.5). For example, dizziness in SSRIs separated significantly from placebo (OR 1.50, 95%CI 1.13-1.99) but had a nocebo index of 0.67. LIMITATIONS: This study relied on multiple RCTs with subtle design differences. CONCLUSIONS: This study identified several AEs that are likely the physiological result of antidepressants and many that likely represent nocebo effects. These results should inform clinical decision making and discussions with patients.

The association between suicide deaths and putatively harmful and protective factors in media reports.

BACKGROUND: Exposure to media reporting on suicide can lead to suicide contagion and, in some circumstances, may also lead to help-seeking behaviour. There is limited evidence for which specific characteristics of media reports mediate these phenomena. METHODS: This observational study examined associations between putatively harmful and protective elements of media reports about suicide in 13 major publications in the Toronto media market and subsequent suicide deaths in Toronto (2011-2014). We used multivariable logistic regression to determine whether specific article characteristics were associated with increases or decreases in suicide deaths in the 7 days after publication, compared with a control window. RESULTS: From 2011 to 2014, there were 6367 articles with suicide as the major focus and 947 suicide deaths. Elements most strongly and independently associated with increased suicides were a statement about the inevitability of suicide (odds ratio [OR] 1.97, confidence interval [CI] 1.07-3.62), about asphyxia by a method other than car exhaust (OR 1.72, CI 1.36-2.18), about suicide by jumping from a building (OR 1.70, CI 1.28-2.26) or about suicide pacts (OR 1.63, CI 1.14-2.35), or a headline that included the suicide method (OR 1.41, CI 1.07-1.86). Elements most strongly and independently associated with decreased suicides were unfavourable characteristics (negative judgments about the deceased; OR 1.85, CI 1.20-2.84), or mentions of railway (OR 1.61, CI 1.10-2.36) and cutting or stabbing (OR 1.59, CI 1.19-2.13) deaths, and individual murder-suicide (OR 1.50, CI 1.23-1.84). INTERPRETATION: This large study identified significant associations between several specific elements of media reports and suicide deaths. It suggests that reporting on suicide can have a meaningful impact on suicide deaths and that journalists and media outlets and organizations should carefully consider the specific content of reports before publication.

Appetitive Symptoms Differentially Predict Treatment Response to Fluoxetine, Light, and Placebo in Nonseasonal Major Depression.

OBJECTIVE: We previously reported that morning bright light therapy is efficacious in adults with nonseasonal major depressive disorder (MDD), both on its own and in combination with fluoxetine. Given that appetitive symptoms predict response to bright light therapy in seasonal depression, we examined, in this secondary analysis, whether the same held true in these nonseasonal MDD patients. METHODS: Data were collected from October 7, 2009, to March 11, 2014. One hundred twenty-two patients who met DSM-IV-TR criteria for MDD without a seasonal pattern were randomly assigned to light monotherapy, fluoxetine, combination light and fluoxetine, or double-placebo (inactivated negative ion generator plus placebo pill). Multiple regression assessed the percentage change in Montgomery-Asberg Depression Rating Scale (MADRS) scores based on treatment condition, appetitive symptom score at baseline (sum of 4 items on the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders version), and the condition-by-appetitive score interaction. Sex was considered as a possible moderator of these effects. RESULTS: The overall regression model predicting treatment response was highly significant (P < .001), and the treatment condition-by-appetitive score interaction was a strong predictor of MADRS change scores (t = 2.65, P = .009). For individuals in the placebo group, more appetitive symptoms at baseline predicted less decrease in MADRS scores at 8 weeks (r = -0.37; large effect size). In contrast, for individuals in the active treatment groups, more appetitive symptoms at baseline predicted more of a decrease in depression scores at 8 weeks (fluoxetine group r = +0.23, medium effect size; light therapy group r = +0.11, small effect size; combination group r = +0.32, medium to large effect size). No moderation effect of sex was found. CONCLUSIONS: More severe appetitive symptoms at baseline predicted treatment response differentially across the 4 treatment groups. Contrary to prior findings in seasonal depression, this association was not robust for MDD patients receiving light therapy alone, although it was stronger in patients receiving fluoxetine with or without light. As the group sample sizes were modest, the current findings should be considered as preliminary only. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00958204.

Ketamine augmentation for major depressive disorder and suicidal ideation: Preliminary experience in an inpatient psychiatry setting.

BACKGROUND: Ketamine is known to rapidly reduce depressive symptoms and suicidal ideation (SI) in patients with major depressive disorder (MDD), but evidence is limited for its acceptability and effectiveness in "real-world" settings. This case series examines serial ketamine infusions in reducing SI and depression scores in adults with MDD admitted to a tertiary care hospital. METHODS: Five inpatients with MDD and SI admitted to hospital in Toronto, Canada received six infusions of 0.5 mg/kg intravenous (IV) ketamine (n = 5) over approximately 12 days, in addition to treatment-as-usual. Suicide and depression rating scores (Scale for Suicidal Ideation, SSI; Montgomery-Åsberg Depression Rating Scale, MADRS) were obtained at baseline, on treatment days, on days 14 and 42 (primary endpoint). RESULTS: All patients experienced benefit with ketamine. SSI scores diminished by 84% from 14.0 ±â€¯4.5 at baseline to 2.2 ±â€¯2.5 at study endpoint. MADRS scores diminished by 47% from 42.2 ±â€¯5.3 at baseline to 22.4 ±â€¯8.0. Two patients withdrew from the study, one to initiate electroconvulsive therapy and one due to an adverse event (dissociative effects) during the ketamine infusion. LIMITATIONS: The major limitation of this study is the small sample size. DISCUSSION: These preliminary pilot data are promising with a greater than two-fold reduction in SI following ketamine infusions. They demonstrate that six serial ketamine infusions may be safe and feasible. These findings support the need for large scale randomized controlled trials to confirm the efficacy of serial ketamine for treatment of SI in "real-world" settings.

Antidepressant effects of focused ultrasound induced blood-brain-barrier opening.

In many cases, hippocampal neurogenesis appears to be a hallmark of antidepressant treatments. One novel technique for inducing this type of neurogenesis is using focused ultrasound waves, in conjunction with circulating microbubbles, to open the blood-brain-barrier. The present experiment aimed to test whether this technique has antidepressant effects in a rodent model. Rats were subjected to 1, 2 or 3 weekly treatments of magnetic resonance-guided focused ultrasound in order to open the blood-brain-barrier in the hippocampal region. Before and after treatments, animals went through modified forced swim tests. 1 week after the final treatment, animals that received 2 weekly treatments showed antidepressant-like effects on behavioural measures in comparison to untreated controls. This was not the case for animals that received 1 or 3 weekly treatments. Effects had disappeared by 5 weeks following the first ultrasound treatment. These results suggest that focused ultrasound may be used for inducing short-term antidepressant effects.

Satisfaction with Mental Health Navigation Services: Piloting an Evaluation with a New Scale.

As mental health navigation services continue to be implemented, the need for valid and reliable tools to assess the quality of these services increases. While case managers target individuals with severe mental illness and aim to reduce burden and cost, and increase independence, navigation services target all individuals with a range of mental health and/or substance use issues, with the aim of reducing barriers to treatment and coordinating individualized care. The current study evaluated satisfaction with a navigation service using a new 22-item questionnaire, the Navigation Satisfaction Tool (NAVSAT). Forty clients completed a web-based version of the NAVSAT to evaluate satisfaction with a family mental health navigation service in Toronto, Canada. Descriptive statistics on the sample and range of treatments/services are provided. The NAVSAT has excellent reliability (Cronbach's alpha = 0.96) and face validity. Satisfaction with the following navigation-level factors were the best predictors of overall satisfaction with navigation; the navigator's ability to recommend the appropriate treatment (ß = 0.116, p = .05), intake procedures (ß = 0.364, p = .005), and the principal contact's satisfaction with his/her frequency of contact with the navigator (ß = 0.602, p = .001). Satisfaction with the following provider-level factors were the best predictors of overall satisfaction with the referred service; the referred service's ability to improve the youth's well being (ß = 0.684, p < .001), and the referred service's ability to listen and understand the family's concerns (ß = 0.356, p = .001). The NAVSAT appears to be a reliable tool for measuring satisfaction in the current sample. If these findings are replicated in a larger population serving youth and young adults in transition, the NAVSAT may prove to be a helpful guide for program evaluation and development for navigation and treatment services for this population.

Did the suicide barrier work after all? Revisiting the Bloor Viaduct natural experiment and its impact on suicide rates in Toronto.

OBJECTIVE: This research aims to determine the long-term impact of the Bloor Street Viaduct suicide barrier on rates of suicide in Toronto and whether media reporting had any impact on suicide rates. DESIGN: Natural experiment. SETTING: City of Toronto, Canada; records at the chief coroner's office of Ontario 1993-2003 (11 years before the barrier) and 2004-2014 (11 years after the barrier). PARTICIPANTS: 5403 people who died by suicide in the city of Toronto. MAIN OUTCOME MEASURE: Changes in yearly rates of suicide by jumping at Bloor Street Viaduct, other bridges including nearest comparison bridge and walking distance bridges, and buildings, and by other means. RESULTS: Suicide rates at the Bloor Street Viaduct declined from 9.0 deaths/year before the barrier to 0.1 deaths/year after the barrier (incidence rate ratio (IRR) 0.005, 95% CI 0.0005 to 0.19, p=0.002). Suicide deaths from bridges in Toronto also declined significantly (IRR 0.53, 95% CI 0.40 to 0.71, p<0.0001). Media reports about suicide at the Bloor Street Viaduct were associated with an increase in suicide-by-jumping from bridges the following year. CONCLUSIONS: The current study demonstrates that, over the long term, suicide-by-jumping declined in Toronto after the barrier with no associated increase in suicide by other means. That is, the barrier appears to have had its intended impact at preventing suicide despite a short-term rise in deaths at other bridges that was at least partially influenced by a media effect. Research examining barriers at other locations should interpret short-term results with caution.

Plasma Phosphatidylethanolamine and Triacylglycerol Fatty Acid Concentrations are Altered in Major Depressive Disorder Patients with Seasonal Pattern.

Disturbances in peripheral and brain lipid metabolism, including the omega-3 fatty acid docosahexaenoic acid (DHA), have been reported in major depressive disorder (MDD). However, these changes have yet to be confirmed in MDD with seasonal pattern (MDD-s), a subtype of recurrent MDD. The present exploratory study quantified plasma plasmalogen and diacyl-phospholipid species, and fatty acids within total phospholipids, cholesteryl esters, triacylglycerols and free fatty acids in non-medicated MDD-s participants (n = 9) during euthymia in summer or fall, and during depression in winter in order to screen for potential high sensitivity lipid biomarkers. Triacylglycerol alpha-linolenic acid concentration was significantly decreased, and myristoleic acid concentration was significantly increased, during winter depression compared to summer-fall euthymia. 1-stearyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine, a diacyl-phospholipid containing stearic acid and DHA, was significantly decreased in winter depression. Concentrations of cholesteryl ester oleic acid and several polyunsaturated fatty acids between summer/fall and winter increased in proportion to the increase in depressive symptoms. The observed changes in lipid metabolic pathways in winter-type MDD-s offer new promise for lipid biomarker development.

Altered soluble epoxide hydrolase-derived oxylipins in patients with seasonal major depression: An exploratory study.

Many cytochrome p450-derived lipids promote resolution of inflammation, in contrast to their soluble epoxide hydrolase(sEH)-derived oxylipin breakdown products. Here we compare plasma oxylipins and precursor fatty acids between seasons in participants with major depressive disorder with seasonal pattern (MDD-s). Euthymic participants with a history of MDD-s recruited in summer-fall were followed-up in winter. At both visits, a structured clinical interview (DSM-5 criteria) and the Beck Depression Inventory II (BDI-II) were administered. Unesterified and total oxylipin pools were assayed by liquid chromatography tandem mass-spectrometry (LC-MS/MS). Precursor fatty acids were measured by gas chromatography. In nine unmedicated participants euthymic at baseline who met depression criteria in winter, BDI-II scores increased from 4.9±4.4 to 19.9±7.7. Four sEH-derived oxylipins increased in winter compared to summer-fall with moderate to large effect sizes. An auto-oxidation product (unesterified epoxyketooctadecadienoic acid) and lipoxygenase-derived 13-hydroxyoctadecadienoic acid also increased in winter. The cytochrome p450-derived 20-COOH-leukotriene B4 (unesterified) and total 14(15)-epoxyeicosatetraenoic acid, and the sEH-derived 14,15-dihydroxyeicostrienoic acid (unesterified), decreased in winter. We conclude that winter depression was associated with changes in cytochrome p450- and sEH-derived oxylipins, suggesting that seasonal shifts in omega-6 and omega-3 fatty acid metabolism mediated by sEH may underlie inflammatory states in symptomatic MDD-s.

Self-poisoning suicide deaths in people with bipolar disorder: characterizing a subgroup and identifying treatment patterns.

OBJECTIVE: To characterize self-poisoning suicide deaths in BD compared to other suicide decedents. METHODS: Extracted coroner data from all suicide deaths (n = 3319) in Toronto, Canada from 1998 to 2012. Analyses of demographics, clinical history, recent stressors, and suicide details were conducted in 5 subgroups of suicide decedents: BD self-poisoning, BD other methods, non-BD self-poisoning, non-BD other methods, and unipolar depression self-poisoning. Toxicology results for lethal and present substances were also compared between BD and non-BD self-poisoning subgroups as well as between BD and unipolar depression self-poisoning subgroups. RESULTS: Among BD suicide decedents, self-poisoning was significantly associated with female sex, past suicide attempts, and comorbid substance abuse. In both the BD and non-BD self-poisoning groups, opioids were the most common class of lethal medication. For both groups, benzodiazepines and antidepressants were the most common medications present at time of death, and in 23% of the BD group, an antidepressant was present without a mood stabilizer or antipsychotic. Only 31% of the BD group had any mood stabilizer present, with carbamazepine being most common. No antidepressant, mood stabilizer, or antipsychotic was present in 15.5% of the BD group. Relative to unipolar depression self-poisoning group, the BD self-poisoning group evidenced higher proportion of previous suicide attempt(s) and psychiatry/ER visits in the previous week. CONCLUSION: People with BD who die by suicide via self-poisoning comprise a distinct but understudied group. The predominant absence of guideline-concordant pharmacologic care comprises a crucial target for future policy and knowledge translation efforts.

Inflammatory Markers and Brain-Derived Neurotrophic Factor as Potential Bridges Linking Bipolar Disorder and Cardiovascular Risk Among Adolescents.

OBJECTIVE: Bipolar disorder (BD) is associated with increased rates of cardiovascular disease (CVD). Brain-derived neurotrophic factor (BDNF) and inflammatory markers are leading biomarkers in BD. We examined whether these biomarkers underlie the link between BD and CVD proxies among adolescents with bipolar spectrum disorders. METHODS: Subjects were 60 adolescents, 13-19 years old (40 with BD and 20 healthy controls [HCs]). Semistructured interviews determined diagnoses based on DSM-IV. Serum was assayed for BDNF, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Carotid intima media thickness (cIMT) and flow-mediated dilation were assessed using ultrasound. Procedures were conducted at a subspecialty clinic (January 2011-May 2014). RESULTS: Adolescents with BD had significantly greater waist circumference (BD: 81.72 cm [11.67 cm], HC: 75.64 cm [8.63 cm]; U = 547.5, P = .021), body mass index (BMI) (BD: 25.50 kg/m²undefined[5.29 kg/m²], HC: 21.76 kg/m² [3.43 kg/m²]; U = 608.5, P < .0001), pulse pressure (BD: 42.31 mm Hg [10.57 mm Hg], HC: 33.84 mm Hg [6.69 mm Hg]; U = 561.5, P < .001), and IL-6 (BD: 8.93 pg/mL [7.71 pg/mL], HC: 4.96 pg/mL [6.38 pg/mL]; U = 516.0, P < .0001) than HC adolescents. Subjects with BD-I (n = 14) and BD-II (n = 16) had greater IL-6 versus HCs (F3,51 = 5.29, P = .003). Controlling for BMI and age did not alter these findings. IL-6 was higher in symptomatic (n = 19) and asymptomatic BD (n = 21) versus that found in HCs (F2,52 = 7.96, P = .001). In symptomatic BD, lower BDNF was associated with greater mean cIMT (ρ = -0.507, P = .037). CONCLUSIONS: This study found evidence of increased inflammation among adolescents with BD. While present findings suggest a potential interplay between symptomatic status, biomarkers, and atherosclerosis proxies, there were no significant differences in cIMT or flow-mediated dilation in adolescents with BD compared to HCs. This may indicate that there is potential opportunity for CVD prevention strategies in adolescents with BD.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. METHODS: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Pharmacological Treatments" is the third of six sections of the 2016 guidelines. With little new information on older medications, treatment recommendations focus on second-generation antidepressants. RESULTS: Evidence-informed responses are given for 21 questions under 4 broad categories: 1) principles of pharmacological management, including individualized assessment of patient and medication factors for antidepressant selection, regular and frequent monitoring, and assessing clinical and functional outcomes with measurement-based care; 2) comparative aspects of antidepressant medications based on efficacy, tolerability, and safety, including summaries of newly approved drugs since 2009; 3) practical approaches to pharmacological management, including drug-drug interactions and maintenance recommendations; and 4) managing inadequate response and treatment resistance, with a focus on switching antidepressants, applying adjunctive treatments, and new and emerging agents. CONCLUSIONS: Evidence-based pharmacological treatments are available for first-line treatment of MDD and for management of inadequate response. However, given the limitations of the evidence base, pharmacological management of MDD still depends on tailoring treatments to the patient.